title: Exploring leptin antagonism in ophthalmic cell models.
abstract: BACKGROUND
  Emerging evidence suggests that angiogenic and pro-inflammatory cytokine leptin might be implicated in ocular neovascularization. However, the potential of inhibiting leptin function in ophthalmic cells has never been explored. Here we assessed mitogenic, angiogenic, and signaling leptin activities in retinal and corneal endothelial cells and examined the capability of a specific leptin receptor (ObR) antagonist, Allo-aca, to inhibit these functions.
  
  
  RESULTS
  The experiments were carried out in monkey retinal (RF/6A) and bovine corneal (BCE) endothelial cells. Leptin at 50-250 ng/mL stimulated the growth of both cell lines in a dose-dependent manner. The maximal mitogenic response (35±7 and 27±3% in RF6A and BCE cells, respectively) was noted at 24 h of 250 ng/mL leptin treatments. Leptin-dependent proliferation was reduced to base levels with 10 and 100 nM Allo-aca in BCE and RF6A cells, respectively. In both cell lines, leptin promoted angiogenic responses, with the maximal increase in tube formation (163±10 and 133±8% in RF6A and BCE cultures, respectively) observed under a 250 ng/mL leptin treatment for 3 h. Furthermore, in both cell lines 250 ng/mL leptin modulated the activity or expression of several signaling molecules involved in proliferation, inflammatory activity and angiogenesis, such as STAT3, Akt, and ERK1/2, COX2, and NFκB. In both cell lines, leptin-induced angiogenic and signaling responses were significantly inhibited with 100 nM Allo-aca. We also found that leptin increased its own mRNA and protein expression in both cell lines, and this autocrine effect was abolished by 100-250 nM Allo-aca.
  
  
  CONCLUSIONS
  Our data provide new insights into the role of leptin in ocular endothelial cells and represent the first original report on targeting ObR in ophthalmic cell models.
authors.affiliation: Sbarro Institute for Cancer Research and Molecular Medicine, Biotechnology Center, Temple University, Philadelphia, Pennsylvania, United States of America.
authors.forename: Laura
authors.initials: L
authors.lastname: Scolaro
authors.forename: Cristina
authors.initials: C
authors.lastname: Parrino
authors.forename: Roberta
authors.initials: R
authors.lastname: Coroniti
authors.forename: Laszlo
authors.initials: L
authors.lastname: Otvos
authors.forename: Eva
authors.initials: E
authors.lastname: Surmacz
mesh_terms: D000818:Animals; D002417:Cattle; D003315:Cornea / Q000378:metabolism / Q000473:pathology; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D000882:Haplorhini; D042541:Intracellular Space / Q000378:metabolism; D020738:Leptin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D009389:Neovascularization, Pathologic / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects; D057786:Peptidomimetics / Q000737:chemistry / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D054411:Receptors, Leptin / Q000037:antagonists & inhibitors*; D012160:Retina / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D020738:Leptin; D057786:Peptidomimetics; D012333:RNA, Messenger; D054411:Receptors, Leptin